Lipid Effects of a Moderate Fat vs. Low Fat Diet among Free Living

Individuals with Metabolic Syndrome: DMetS Extension

Arthi Thirumalai, M.D.

Alice Dowdy M.S., Brian Fish, B.S., Robert H. Knopp, M.D., Pathmaja Paramsothy, M.D. M.S.

Global Purpose

To understand what diet is best and most feasible to decrease CVD risk factors among people with metabolic syndrome (MetS)

ObjectivesDetermine if the lipid improvements noted with a

moderate fat, moderate carbohydrate diet vs. low fat, high carbohydrate diet can be sustained under free-living conditions

Determine if free living people with MetS can adhere to prescribed diets on their own

The Problem: Metabolic Syndrome

30% of Americans have MetS

2 fold ↑ risk for CVD

Poor diet results in MetS

Weight loss is the ideal treatment but success rate is low

Refs: Grundy SM et al. Circulation. 2004;109:433-438, Lutsey P et al. Circulation. 2008;117:754-761. Gami AS et al. J Am Coll Cardiol. 2007;49:403-414

Metabolic Syndrome

Triglycerides ≥ 150 mg/dL PLUS 2 of:

HDL-C < 40 (men), < 50 mg/dL (women)

Blood Pressure ≥ 130/85 (or on antihypertensive meds)

Fasting Glucose > 100 mg/dL

Abdominal Obesity

Waist circumference >102 cm (men), > 88 cm (women)

Current Dietary Recommendations

Total fat 20-35%, total carbohydrate 45-65%

<10% saturated fat

Negligible trans fat

Insulin Resistant Populations such as those with MetS are not adequately addressed

What type of fats is unclear

Source: Dietary Guidelines for Americans, 2010

Maintaining free-living diets

No studies investigating the effects of a truly free-living diet on lipid effects or feasibility in MetS

Either employed food-exchange models or studied ad libitum diets in non-MetS patients

High drop-out rates: 12-40%

High tendency to not achieve dietary targets

Diets for Dyslipidemia in Metabolic Syndrome (DMetS)

Study Design: Double blinded, randomized, X-over

Intervention:

Moderate Fat (MF) = 40% fat, 45% carbohydrate

Low fat (LF) = 20% fat, 65% carbohydrate

Both diets 15% protein, 8% saturated fat, 25-30 g/day of fiber

Primary Lipid Outcome: Δ Non-HDL cholesterol from baseline

Also evaluated inflammatory markers, endothelial function, glycemic indices

Exclusion Criteria

LDL-C > 190 mg/dL

Triglyceride > 500 mg/dL

BP > 150/95 mmHg mean 2 visits

Use of lipid lowering rx other than statins

Moderate or high doses of thiazides or beta blockers previous 4 weeks

Use of plant sterols previous 4 weeks

Use of diabetes rx or fasting glucose level > 140 mg/dL

Hospitalization for CHD within 6 months

Summary Lipid Changes

DMetS: Results Summary

o First randomized controlled feeding study comparing LF vs. MF diet in MetS

o MF diet improves the atherogenic dyslipidemia of MetS compared with LF diet

o No significant difference in inflammatory markers, insulin sensitivity, or endothelial function

Study Design

Extension period:- 63 subjects (32 LF, 31 MF)- Weekly dietary sessions and counselling- Food records collected using 24 hour dietary recall

Statistical methods

Hypothesis 1: Subjects will be able to sustain their diet during the extension period as measured by lipid effectsPaired T-Tests

Hypothesis 2: The difference in effects of MF vs LF diets on atherogenic dyslipidemia of MetS will be maintained during the extension period Unpaired T-Tests

RESULTS

Baseline characteristics

Lipid outcomes Primary outcome: ∆ non-HDLc from end of

controlled feeding to end of free-living extension period

Secondary outcomes: ∆ Total cholesterol, ∆ triglycerides, ∆ HDLc, ∆ LDLc, ∆ Apo-B, ∆ Apo-A1

Adherence rates

Baseline characteristicsVariable Low Fat Moderate Fat P (MF vs LF)

Age (years) 55.7 51.9 0.06

Women 56% 48% 0.62

White race 88% 90% >0.99

BMI (kg/m2) 30.3 (4.09) 30.3 (4.93) 0.98

Waist Circumference (cm) 108 (14.8) 105 (18.5) 0.44

% meeting MetS definition of

HTN34% 29% 0.62

Triglycerides (mg/dL)* 232 [187,269] 181 [138,216] 0.02*

HDL Cholesterol (mg/dL) 38.9 (6.86) 40.7 (8.27) 0.35

Total Cholesterol (mg/dL) 203 (32.2) 189 (31.3) 0.09

Non-HDL Cholesterol (mg/dL)* 164 (29.9) 148 (30.2) 0.04*

LDL Cholesterol (mg/dL) 117 (31.6) 110 (26.9) 0.37

Apolipoprotein B (mg/dL) 113 (20.7) 106 (16.9) 0.14

Apolipoprotein A-I (mg/dL) 120 (15.3) 123 (18.6) 0.46

Glucose (mg/dL) 99.7 (8.88) 102 (9.67) 0.44

∆ Non-HDLc

  Baseline

Mean (SD)

End of extension

period

Mean (SD)

Change during

study period

Mean (SD)

Difference between

diets

Mean (SE) [95% CI]

Low Fat 164 (29.9) 165 (32.6) 1.66 (22.7) p=0.683  

Moderate Fat 148 (30.2)156 (27.9) 7.97 (25.7) p=0.095

 

(MF vs. LF)   

 -6.31 [6.11] [-18.5, 5.91]

p=0.306

∆ Total cholesterol

  Baseline

Mean (SD)

End of extension

period

Mean (SD)

Change during

study period

Mean (SD)

Difference between

diets

Mean (SE) [95% CI]

Low Fat 203 (32.2)207 (32.4)

4.16 (20.8) p=0.268  

Moderate Fat 184 (31.3)198 (29.3)

8.90 (26.3) p=0.069  

P value (MF vs. LF)   

 -4.75 [5.97] [-16.7,7.19]

p=0.430

∆ Triglycerides

  Baseline

Mean (SD)

End of extension

period

Mean (SD)

[median for

skewed items]

Change during

study period

Mean (SD)

Difference between

diets

Mean (SE) [95% CI]

Low Fat 234 (67.8)264 (186) [218]

30.1 (170) p=0.324  

Moderate Fat 190 (83.8)215 (103) [192]

25.6 (104) p=0.179  

P value (MF vs. LF)   

 4.45 [35.5] [-66.6,75.5]

p=0.901

∆ LDLc

  Baseline

Mean (SD)

End of extension

period

Mean (SD)

Change during

study period

Mean (SD)

Difference between

diets

Mean (SE) [95% CI]

Low Fat 117 (31.6)113 (36.4)

-4.28 (22.0) p=0.279  

Moderate Fat 110 (26.9)113 (28.8)

2.90 (26.1) p=0.541  

P value (MF vs. LF)   

 -7.18 [6.08] [-19.3,4.96]

p=0.242

∆ HDLc

  Baseline

Mean (SD)

End of extension

period

Mean (SD)

Change during

study period

Mean (SD)

Difference between

diets

Mean (SE) [95% CI]

Low Fat 38.9 (6.86)41.4 (9.46)

2.50 (5.92) p=0.023  

Moderate Fat 40.7 (8.27)41.6 (7.77)

0.935 (5.38) p=0.341  

P value (MF vs. LF)   

 1.56 [1.43] [-1.29,4.42]

p=0.277

∆ Apo-B

  Baseline

Mean (SD)

End of extension

period

Mean (SD)

Change during

study period

Mean (SD)

Difference between

diets

Mean (SE) [95% CI]

Low Fat 113 (20.7) 114 (18.8)-0.0978 (14.1)

p=0.970 

Moderate Fat106 (16.9) 109 (19.7)

2.73 (13.3) p=0.270  

P value (MF vs. LF)      -2.83 [3.51] [-9.86,4.20]

p=0.423

∆ Apo-A1

  Baseline

Mean (SD)

End of extension

period

Mean (SD)

Change during

study period

Mean (SD)

Difference between

diets

Mean (SE) [95% CI]

Low Fat120 (15.3) 134 (14.9) 13.8 (12.1) p<0.001  

Moderate Fat123 (18.6) 131 (16.8)

7.70 (12.3) p=0.002  

P value (MF vs. LF)      6.07 [3.12] [-0.178,12.3]

p=0.057

Adherence

% calories from

carbohydrate

Mean (SD)[rec]

% calories from protein

Mean (SD)[rec]

% calories from fat

Mean (SD)[rec]

Low Fat53.87 (9.60)

[65]19.91 (5.55)

[15]25.96 (8.50)

[20]

Moderate Fat47.45 (9.92)

[45]17.50 (5.37)

[15]34.58 (8.30)

[40]

Conclusions

First study looking at lipid outcomes in MetS patients at weight stability, under truly free-living conditions

Significantly lower drop out rate compared to prior studies

Able to sustain the benefits noted during controlled feeding phase, even under free-living conditions

No significant difference between the two diets in lipid outcomes likely related to not achieving carbohydrate and fat goals in 2 diets

Acknowledgements

DMetS participants

Northwest Lipid Research Clinic Staff

University of Washington CRC Staff

Alice Dowdy and Brian Fish

Dr. Robert H. Knopp, original PI for DMetS, who passed away on 5/30/10

Dr. Pathmaja Paramsothy, PI and phenomenal mentor!

Thank you